B-vitamins intake, DNA-methylation of One Carbon Metabolism and homocysteine pathway genes and myocardial infarction risk: The EPICOR study

被引：48

作者：

Fiorito, G. ^{[1
,2
]}

Guarrera, S. ^{[1
]}

Valle, C. ^{[1
]}

Ricceri, F. ^{[1
,2
]}

Russo, A. ^{[1
,2
]}

Grioni, S. ^{[3
]}

Mattiello, A. ^{[4
]}

Di Gaetano, C. ^{[1
,2
]}

Rosa, F. ^{[1
]}

Modica, F. ^{[1
]}

Iacoviello, L. ^{[5
]}

Frasca, G. ^{[6
]}

Tumino, R. ^{[6
]}

Krogh, V. ^{[3
]}

Panico, S. ^{[4
]}

Vineis, P. ^{[1
,7
]}

Sacerdote, C. ^{[1
,8
]}

Matullo, G. ^{[1
,2
]}

机构：

[1] Human Genet Fdn, Turin, Italy

[2] Univ Turin, Dept Med Sci, I-10124 Turin, Italy

[3] Fdn IRCSS Ist Nazl Tumori, Dept Prevent & Predict Med, Epidemiol & Prevent Unit, Milan, Italy

[4] Univ Naples Federico II, Dept Clin & Expt Med, Naples, Italy

[5] IRCCS Ist Neurol Mediterraneo Neuromed, Dept Epidemiol & Prevent, Rome, Italy

[6] Civile MP Arezzo Hosp, Canc Registry & Histopathol Unit, Ragusa, Italy

[7] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England

[8] CPO Piemonte, Canc Epidemiol, Turin, Italy

来源：

NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES | 2014年 / 24卷 / 05期

关键词：

DNA-methylation; B-vitamins; Myocardial infarction; One Carbon Metabolism; Homocysteine; CARDIOVASCULAR RISK; HYPERHOMOCYSTEINEMIA; ASSOCIATION; FOLATE; MICE;

D O I：

10.1016/j.numecd.2013.10.026

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background and aims: Several epidemiological studies highlighted the association between folate and B-vitamins low intake and cardiovascular diseases (CVD) risk. Contrasting results were reported on the relationship between folate intake and DNA-methylation. Folate and B-vitamins may modulate DNA-methylation of specific enzymes which are included in the One-Carbon Metabolism (OCM) and in the homocysteine (Hcy) pathways. The aim of the study was to evaluate whether DNA-methylation profiles of OCM and Hcy genes could modulate the myocardial infarction (MI) risk conferred by a low B-vitamins intake. Methods and results: Study sample (206 MI cases and 206 matched controls) is a case-control study nested in the prospective EPIC cohort. Methylation levels of 33 candidate genes where extracted by the whole epigenome analysis (Illumina-HumanMethylation450K-BeadChip). We identified three differentially methylated regions in males (TCN2 promoter, CBS 5'UTR, AMT gene-body) and two in females (PON1 gene-body, CBS 5'UTR), each of them characterized by an increased methylation in cases. Functional in silico analysis suggested a decreased expression in cases. A Recursively Partitioned Mixture Model cluster algorithm identified distinct methylation profiles associated to different MI risk: high-risk vs. low-risk methylation profile groups, OR = 3.49, p = 1.87 x 10(-4) and OR = 3.94, p = 0.0317 in males and females respectively (multivariate logistic regression adjusted for classical CVD risk factors). Moreover, a general inverse relationship between B-vitamins intake and DNA-methylation of the candidate genes was observed. Conclusions: Our findings support the hypothesis that DNA-methylation patterns in specific regions of OCM and Hcy pathways genes may modulate the CVD risk conferred by folate and B-vitamins low intake. (C) 2013 Elsevier B.V. All rights reserved.

引用

页码：483 / 488

页数：6

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